Molecular basis of complement factor I (CFI) polymorphism: one of two polymorphic suballeles responsible for CFI A is Japanese-specific

Isoelectric focusing has revealed that human complement factor I (CFI) is controlled by two polymorphic alleles, CFI*A and CFI*B, and a few rare variant alleles. In this study the molecular basis of the CFI polymorphism was investigated in 174 Japanese. The CFI*A was divided into two suballeles, CFI*As (R201S) and CFI*Ah (R406H). CFI*Aj, a rare variant allele originating from CFI*Ah, had an additional mutation (R502L). The distribution of these three mutations and two registered SNPs was investigated in a total of 2,471 individuals in 20 populations from various areas, and six haplotypes were observed. Haplotype H3, which is characterized by CFI*As, was found only in Far East populations: the frequencies were about 0.03 in the main island of Japan and lower than 0.01 in Okinawa and Korea. Haplotype H5, characterized by CFI*Ah, prevailed almost exclusively in East Asians and was observed at the highest frequencies in southern Chinese Han and Thais. CFI*Ah must have arisen in a southeastern part of Asia and thereafter have spread to neighboring populations.